rs10849441

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384598.1(PLEKHG6):​c.1525-23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,589,732 control chromosomes in the GnomAD database, including 166,781 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.40 ( 12926 hom., cov: 32)
Exomes 𝑓: 0.46 ( 153855 hom. )

Consequence

PLEKHG6
NM_001384598.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.255
Variant links:
Genes affected
PLEKHG6 (HGNC:25562): (pleckstrin homology and RhoGEF domain containing G6) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in cell junction and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLEKHG6NM_001384598.1 linkuse as main transcriptc.1525-23A>G intron_variant ENST00000684764.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLEKHG6ENST00000684764.1 linkuse as main transcriptc.1525-23A>G intron_variant NM_001384598.1 P1Q3KR16-1

Frequencies

GnomAD3 genomes
AF:
0.397
AC:
60251
AN:
151694
Hom.:
12919
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.246
Gnomad AMI
AF:
0.404
Gnomad AMR
AF:
0.364
Gnomad ASJ
AF:
0.411
Gnomad EAS
AF:
0.262
Gnomad SAS
AF:
0.324
Gnomad FIN
AF:
0.582
Gnomad MID
AF:
0.354
Gnomad NFE
AF:
0.484
Gnomad OTH
AF:
0.378
GnomAD3 exomes
AF:
0.414
AC:
102975
AN:
248920
Hom.:
22407
AF XY:
0.417
AC XY:
56189
AN XY:
134738
show subpopulations
Gnomad AFR exome
AF:
0.254
Gnomad AMR exome
AF:
0.333
Gnomad ASJ exome
AF:
0.406
Gnomad EAS exome
AF:
0.254
Gnomad SAS exome
AF:
0.336
Gnomad FIN exome
AF:
0.572
Gnomad NFE exome
AF:
0.478
Gnomad OTH exome
AF:
0.428
GnomAD4 exome
AF:
0.456
AC:
655064
AN:
1437920
Hom.:
153855
Cov.:
28
AF XY:
0.454
AC XY:
325359
AN XY:
716776
show subpopulations
Gnomad4 AFR exome
AF:
0.238
Gnomad4 AMR exome
AF:
0.332
Gnomad4 ASJ exome
AF:
0.403
Gnomad4 EAS exome
AF:
0.279
Gnomad4 SAS exome
AF:
0.344
Gnomad4 FIN exome
AF:
0.575
Gnomad4 NFE exome
AF:
0.480
Gnomad4 OTH exome
AF:
0.428
GnomAD4 genome
AF:
0.397
AC:
60273
AN:
151812
Hom.:
12926
Cov.:
32
AF XY:
0.400
AC XY:
29658
AN XY:
74144
show subpopulations
Gnomad4 AFR
AF:
0.246
Gnomad4 AMR
AF:
0.363
Gnomad4 ASJ
AF:
0.411
Gnomad4 EAS
AF:
0.262
Gnomad4 SAS
AF:
0.324
Gnomad4 FIN
AF:
0.582
Gnomad4 NFE
AF:
0.484
Gnomad4 OTH
AF:
0.382
Alfa
AF:
0.441
Hom.:
5367
Bravo
AF:
0.370
Asia WGS
AF:
0.303
AC:
1055
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.9
DANN
Benign
0.45
BranchPoint Hunter
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10849441; hg19: chr12-6435571; COSMIC: COSV50598978; COSMIC: COSV50598978; API